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-Structure paper
タイトル | Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses. |
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ジャーナル・号・ページ | Immunity, Vol. 54, Issue 4, Page 769-780.e6, Year 2021 |
掲載日 | 2021年4月13日 |
著者 | Maryam Mukhamedova / Daniel Wrapp / Chen-Hsiang Shen / Morgan S A Gilman / Tracy J Ruckwardt / Chaim A Schramm / Larissa Ault / Lauren Chang / Alexandrine Derrien-Colemyn / Sarah A M Lucas / Amy Ransier / Samuel Darko / Emily Phung / Lingshu Wang / Yi Zhang / Scott A Rush / Bharat Madan / Guillaume B E Stewart-Jones / Pamela J Costner / LaSonji A Holman / Somia P Hickman / Nina M Berkowitz / Nicole A Doria-Rose / Kaitlyn M Morabito / Brandon J DeKosky / Martin R Gaudinski / Grace L Chen / Michelle C Crank / John Misasi / Nancy J Sullivan / Daniel C Douek / Peter D Kwong / Barney S Graham / Jason S McLellan / John R Mascola / |
PubMed 要旨 | An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) ...An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV. |
リンク | Immunity / PubMed:33823129 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.9 - 3.21 Å |
構造データ | EMDB-23520, PDB-7luc: EMDB-23521, PDB-7lue: PDB-7lud: |
化合物 | ChemComp-SO4: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRAL PROTEIN / RSV / viral fusogen / fusion protein / antibody / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN complex / RSV F / Fab / Viral fusion protein / VIRAL PROTEIN/IMMUNE SYSTEM / fusion / immunoglobulin / public clonotype / convergent recognition / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |